This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Multicellular organisms consist of various cell types with the same genetic information but a high degree of differentiation, characterized by a unique pattern of gene expression for each cell type. Establishment and maintenance of these diverse expression patterns is fundamentally important for cell identity and organism survival, and aberrant gene expression in a single cell can lead to developmental abnormalities or cancer. Epigenetic regulatory mechanisms employ dynamic modifications in chromatin structure, such as histone methylation, acetylation, phosphorylation and ubiquitination, to regulate gene expression. These posttranslational modifications are integrated in a combinatorial fashion to provide cells with transcriptional memory to stably maintain gene expression patterns throughout many divisions, and developmental flexibility to facilitate programmed alterations in gene expression. Equipped with the unprecedented sensitivity and structural specificity offered by tandem mass spectrometry, we are hoping to elucidate the nature and functional role of the rich epigenetic information in mammalian chromatin.